Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets.

The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocysteine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects. Forty-nine strict vegan subjects were allocated to the oral CrS (5 g micronized creatine monohydrate daily for three weeks; n = 31) and placebo (n = 18) groups. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate cutaneous microvascular reactivity, and intravital video-microscopy was used to evaluate skin capillary density and reactivity before and after CrS. We demonstrated that CrS reduces the plasma levels of homocysteine and increases those of folic acid. After the CrS period, the homocysteine levels of all of the vegan subjects normalized. CrS also induced increases in baseline skin functional capillary density and endothelium-dependent capillary recruitment in both normo- (N-Hcy) and hyperhomocysteinemic (H-Hcy) individuals. CrS increased endothelium-dependent skin microvascular vasodilation in the H-Hcy vegan subjects but not in the N-Hcy vegan subjects. In conclusion, three weeks of oral CrS was sufficient to increase skin capillary density and recruitment and endothelium-dependent microvascular reactivity. CrS also resulted in plasma increases in folic acid levels and reductions in homocysteine levels among only the H-Hcy individuals.

Whey protein supplementation for the preservation of mass and muscular strength of patients with heart failure: study protocol for a randomized controlled trial.

BACKGROUND: Heart failure (HF) is an important public health problem, considered a new epidemic with high morbidity and mortality. The progression of HF often determines weight reduction, muscle mass loss, and reduced physical ability. Whey protein supplementation may increase the effects of exercise on strength and muscle mass, in addition to promoting improved endothelial function, body composition and quality of life. However, studies are needed to evaluate its benefits in patients with HF. METHODS/DESIGN: This is a double-blind, randomized, placebo-controlled clinical trial in which patients with HF will be randomly allocated to two groups to receive supplementation with whey protein or placebo, associated with supervised exercise, for 12 weeks. The frequency of exercise will be three times a week. The study variables will be evaluated at baseline and 12 weeks. The main outcome will be maintenance of muscle mass and strength. Microvascular reactivity, quality of life, and inflammatory parameters will be evaluated as secondary outcomes. DISCUSSION: HF is associated with severe loss of muscle mass and strength, directly contributing to exercise intolerance and inability to maintain daily life activities, becoming a strong predictor of reduced quality of life and mortality. The results of this study will add to the evidence base for providing new dietary recommendations. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03142399 . Registered on 29 May 2016. Effect of Whey Protein' Supplementation and Exercise in Patients with Heart Failure (PROT-HF).

High-intensity interval training or continuous training, combined or not with fasting, in obese or overweight women with cardiometabolic risk factors: study protocol for a randomised clinical trial.

INTRODUCTION: Physical inactivity and increased caloric intake play important roles in the pathophysiology of obesity. Increasing physical activity and modifying eating behaviours are first-line interventions, frequently hampered by lack of time to exercise and difficulties in coping with different diets. High-intensity interval training (HIIT) may be a time-efficient method compared with moderate-intensity continuous training (CT). Conversely, diets with a fasting component may be more effective than other complex and restrictive diets, as it essentially limits caloric intake to a specified period without major diet composition changes. Therefore, the combination of HIIT and fasting may provide incremental benefits in terms of effectiveness and time efficiency in obese and sedentary populations. The aim of this study is to determine the effect of HIIT versus CT, combined or not with fasting, on microcirculatory function, cardiometabolic parameters, anthropometric indices, cardiorespiratory fitness and quality of life in a population of sedentary overweight or obese women with cardiometabolic risk factors. METHODS AND ANALYSIS: Sedentary women aged 30-50 years, with a body mass index ≥25 kg/m2 and cardiometabolic risk factors, will be randomised to HIIT performed in the fasting state, HIIT performed in the fed state, CT in the fasting state or CT in the fed state. Cardiometabolic parameters, anthropometric indices, cardiorespiratory fitness, quality of life and microvascular function (cutaneous capillary density and microvascular reactivity evaluated by laser speckle contrast imaging) will be evaluated before initiation of the interventions and 16 weeks thereafter. ETHICS AND DISSEMINATION: The trial complies with the Declaration of Helsinki and has been approved by the local ethics committee (Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil). All patients provide written informed consent before enrolment and randomisation. The study's results will be disseminated to the healthcare community by publications and presentations at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03236285.

Effects of Riot Control Training on Systemic Microvascular Reactivity and Capillary Density.

Introduction: The main aim of the present study is to evaluate the effects of strenuous exercise, related to special military training for riot control, on systemic microvascular endothelial function and skin capillary density. Materials and Methods: Endothelium-dependent microvascular reactivity was evaluated in the forearm skin of healthy military trainees (age 23.4 ± 2.3 yr; n = 15) using laser speckle contrast imaging coupled with cutaneous acetylcholine (ACh) iontophoresis and post-occlusive reactive hyperemia (PORH). Functional capillary density was assessed using high-resolution, intra-vital color microscopy in the dorsum of the middle phalanx. Capillary recruitment (capillary reserve) was evaluated using PORH. Microcirculatory tests were performed before and after a 5-wk special military training for riot control. Results: Microvascular endothelium-dependent vasodilatory responses were markedly and significantly reduced after training, compared with values obtained before training. The peak values of microvascular conductance obtained during iontophoresis of ACh or PORH before training (0.84 ± 0.22 and 0.94 ± 0.72 APU/mmHg, respectively) were markedly reduced after training (0.47 ± 0.11 and 0.71 ± 0.14 APU/mmHg; p < 0.0001 and p = 0.0037, respectively). Endothelium-dependent capillary recruitment was significantly reduced after training (before 101 ± 9 and after 95 ± 8 capillaries/mm2; p = 0.0007). Conclusions: The present study showed that a 5-wk strenuous military training, performed in unfavorable climatic conditions, induces marked systemic microvascular dysfunction, mainly characterized by reduced endothelium-dependent microvascular vasodilation and blunted capillary recruitment.

Early Functional and Structural Microvascular Changes in Hypertension Related to Aging.

It is becoming increasingly clear that both microvascular network alterations and subsequent tissue perfusion defects may precede and predict the development of arterial hypertension and other cardiovascular and metabolic diseases, including diabetes and metabolic syndrome. Moreover, the subsequent functional and structural alterations in microvascular reactivity and density, as well as alterations in the macrocirculation characteristic of physiologic vascular aging, contribute to the development of target organ damage. Microvascular rarefaction appears to be an early vascular structural alteration in the setting of hypertension, as it is already present in individuals presenting with borderline hypertension and normotensive young adults with a familial predisposition to high blood pressure. The chronic increases in blood pressure that occur during senescence secondary to macrocirculatory changes induce vasoconstriction within the microcirculation, which promotes the development of tissue hypoxia and reduces both arteriolar and capillary density. This phenomenon contributes to additional increases in peripheral vascular resistance and establishes a vicious cycle that culminates in both tissue injury and target organ damage, which are equally present in senescence and hypertension. Therefore, the microcirculation may be considered an essential target for both the pharmacological and non-pharmacological treatment of arterial hypertension and other cardiovascular diseases.

Effects of non-supervised low intensity aerobic excise training on the microvascular endothelial function of patients with type 1 diabetes: a non-pharmacological interventional study.

BACKGROUND: The aim of the present study was to evaluate changes in microvascular density and reactivity in patients with type 1 diabetes (T1D) resulting from low intensity chronic exercise training. METHODS: This study included 22 (34 ± 7 ears) consecutive outpatients with T1D and disease duration > 6 years. We used intravital video-microscopy to measure basal skin capillary density and capillary recruitment using post-occlusive reactive hyperemia (PORH) in the dorsum of the fingers. Endothelium-dependent and -independent vasodilation of the skin microcirculation was evaluated in the forearm with a laser Doppler flow monitoring (LDF) system in combination with acetylcholine and sodium nitroprusside iontophoresis, PORH and local thermal hyperemia. RESULTS: The basal mean capillary density (MCD) after exercise training was significantly higher than before exercise (134 ± 25 vs. 119 ± 19 capillaries/mm(2), respectively; P = 0.0013). MCD during PORH was also higher after exercise (140 ± 26 vs. 121 ± 24 capillaries/mm(2), respectively; P < 0.0001). Endothelium-dependent capillary recruitment during PORH was also significantly higher after exercise (140 ± 26 vs. 134 ± 25 capillaries/mm(2), respectively; P < 0.0012). There were no significant changes in skin microvascular reactivity after exercise as investigated using LDF. CONCLUSIONS: Our results showed that low intensity aerobic exercise, performed four times per week for 12 weeks by patients with T1D, induces significant increases in microvascular density and endothelial-dependent capillary reactivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02441504. Registered 7 May 2015.

Interval and continuous exercise training produce similar increases in skeletal muscle and left ventricle microvascular density in rats.

Interval training (IT), consisting of alternated periods of high and low intensity exercise, has been proposed as a strategy to induce more marked biological adaptations than continuous exercise training (CT). The purpose of this study was to assess the effects of IT and CT with equivalent total energy expenditure on capillary skeletal and cardiac muscles in rats. Wistar rats ran on a treadmill for 30 min per day with no slope (0%), 4 times/week for 13 weeks. CT has constant load of 70% max; IT has cycles of 90% max for 1 min followed by 1 min at 50% max. CT and IT increased endurance and muscle oxidative capacity and attenuated body weight gain to a similar extent (P > 0.05). In addition, CT and IT similarly increased functional capillary density of skeletal muscle (CT: 30.6 ± 11.7%; IT: 28.7 ± 11.9%) and the capillary-to-fiber ratio in skeletal muscle (CT: 28.7 ± 14.4%; IT: 40.1 ± 17.2%) and in the left ventricle (CT: 57.3 ± 53.1%; IT: 54.3 ± 40.5%). In conclusion, at equivalent total work volumes, interval exercise training induced similar functional and structural alterations in the microcirculation of skeletal muscle and myocardium in healthy rats compared to continuous exercise training.

Evaluation of systemic microvascular endothelial function using laser speckle contrast imaging.

OBJECTIVE: The aim of this study was to compare cutaneous microvascular function in young healthy subjects (n=50) with that of cardiometabolic diseased patients (n=50) using laser speckle contrast imaging (LSCI) coupled with transdermal iontophoretic delivery of acetylcholine (ACh) and post-occlusive reactive hyperemia (PORH). METHODS: Cutaneous blood flow was assessed in the forearm using LSCI at rest, during PORH and during iontophoresis of ACh with increasing anodal currents of 30, 60, 90, 120, 150 and 180 µA during 10-second intervals spaced 1 min apart. RESULTS: Endothelium-dependent skin microvascular vasodilator responses induced by both ACh and PORH were significantly reduced in cardiometabolic diseased patients compared to healthy subjects. Vasodilator responses induced by ACh were significantly higher in young women than in young men. Iontophoresis charges up to 1.5 mC do not induce nonspecific effects on skin microvascular flux. CONCLUSION: LSCI appears to be a promising noninvasive technique for evaluating systemic microvascular endothelial function.

Exercise training protects the renal circulation against high glucose challenge.

It has been shown previously that high glucose causes direct and acute endothelial dysfunction in non-diabetic isolated rabbit kidney. This study assessed whether exercise training is able to maintain normal renal vascular endothelial function despite high glucose exposure. Animals were pen confined (SED) or treadmill trained over a 12-week period (ExT). Kidneys isolated from SED and ExT rabbits were continuously perfused ex vivo during 3 h with Krebs-Henseleit solutions containing normal (5.5 mm) or high (15 mm) concentrations of d-glucose. In the SED 5.5 group, acetylcholine (ACh) induced dose-related vasodilator responses, reaching the maximum of 41+/- 2% (n=10; P<0.05). In the kidneys perfused with high concentrations of glucose (SED 15), endothelium-dependent vasodilation was significantly blunted. Maximal relaxation in the presence of 15 mm glucose was of 19 +/- 2%, which was significantly different from the SED 5.5 group (41+/- 2%, n=10, P<0.01). In the ExT 5.5 group, ACh-induced vasodilation was significantly enhanced when compared with the SED 5.5 group, reaching the maximum of (52+/- 2%, n=10, P<0.05). Moreover, the exposure of the renal circulation of ExT animals to high glucose did not change endothelium-dependent vasodilation induced by ACh (46+/- 3%, n=6), when compared with the ExT 5.5 group. Finally, exercise training prevented the deleterious effects of high glucose on endothelial-dependent renal vasodilation (SED 15: 19+/- 2% vs. ExT 15: 46+/- 3%; P<0.05). It is concluded that exercise training protects the rabbit renal circulation against endothelial dysfunction elicited by acute exposure to moderately elevated glucose levels, corresponding to the postprandial glycemia of diabetes type 2 patients under treatment. The enhanced renal vasodilator reserve elicited by exercise training turns out to be a response that protects the kidney from the deleterious effects of glycemic peaks.

Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits.

Exercise training is known to improve vasodilating mechanisms mediated by endothelium-dependent relaxing factors in the cardiac and skeletal muscle vascular beds. However, the effects of exercise training on visceral vascular reactivity, including the renal circulation, are still unclear. We used the experimental model of the isolated perfused rabbit kidney, which involves both the renal macro- and microcirculation, to test the hypothesis that exercise training improves vasodilator mechanisms in the entire renal circulation. New Zealand White rabbits were pen confined (Sed; n = 24) or treadmill trained (0% grade) for 5 days/wk at a speed of 18 m/min during 60 min over a 12-wk period (ExT; n = 24). Kidneys isolated from Sed and ExT rabbits were continuously perfused in a nonrecirculating system under conditions of constant flow and precontracted with norepinephrine (NE). We assessed the effects of exercise training on renal vascular reactivity using endothelial-dependent [acetylcholine (ACh) and bradykinin (BK)] and -independent [sodium nitroprusside (SNP)] vasodilators. ACh induced marked and dose-related vasodilator responses in kidneys from Sed rabbits, the reduction in perfusion pressure reaching 41 +/- 8% (n = 6; P < 0.05). In the kidneys from ExT rabbits, vasodilation induced by ACh was significantly enhanced to 54 +/- 6% (n = 6; P < 0.05). In contrast, BK-induced renal vasodilation was not enhanced by training [19 +/- 8 and 13 +/- 4% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n = 6; P > 0.05)]. Continuous perfusion of isolated kidneys from ExT animals with N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM), an inhibitor of nitric oxide (NO) biosynthesis, completely blunted the additional vasodilation elicited by ACh [reduction in perfusion pressure of 54 +/- 6 and 38 +/- 5% for ExT and L-NAME + ExT, respectively (n = 6; P < 0.05)]. On the other hand, L-NAME infusion did not affect ACh-induced vasodilation in Sed animals. Exercise training also increased renal vasodilation induced by SNP [36 +/- 7 and 45 +/- 10% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n = 6; P < 0.05)]. It is concluded that exercise training alters the rabbit kidney vascular reactivity, enhancing endothelium-dependent and -independent renal vasodilation. This effect seems to be related not only to an increased bioavailability of NO but also to the enhanced responsiveness of the renal vascular smooth muscle to NO.